What are vasomotor symptoms?

The medical term for hot flashes and night sweats. They begin for many women in the years leading up to menopause and can continue after it. A pooled analysis of population studies put the share of women affected at about 54% to 74%, depending on the region.

What does the new guideline recommend?

The American College of Physicians recommends estrogen as the first treatment for women who want one, combined with a progestogen for those who have a uterus. For women who cannot take estrogen it suggests venlafaxine or desvenlafaxine next, then escitalopram, paroxetine, gabapentin, elinzanetant or fezolinetant.

Do the non-hormonal drugs work?

In the review, several of them reduced how often hot flashes occurred compared with placebo, but not how severe they were. In two trials of elinzanetant, women taking it had about three fewer moderate or severe episodes a day than women on placebo after 12 weeks.

What did the review find about harms?

Few serious adverse events were reported in the trials. Most trials were short and were not designed to detect serious or long-term harms, and studies that follow women for years in ordinary practice were not part of the review.

Does the guideline apply to every woman with hot flashes?

No. It asks clinicians to discuss benefits, harms, other health conditions, preferences and cost with each patient. Which treatment, if any, suits a particular woman is assessed by her doctor. This is general information rather than medical advice.

Hormone therapy is first choice for hot flashes in a new US guideline built on a review of 90 trials

The American College of Physicians ranks estrogen first, two antidepressants second and five other drugs third. Its evidence review found most trials short, with little on long-term harms and few head-to-head comparisons.

Hot flashes and night sweats are the symptoms that most often send women to a doctor around menopause, and the list of medicines on offer has grown. Two new non-hormonal pills have reached the market in recent years. Regulators in the United States have softened the warnings on hormone products. What had been missing was a ranking.

The American College of Physicians (ACP), which represents internal medicine doctors in the United States, has now supplied one. Its guideline, published in Annals of Internal Medicine in the first week of October, puts estrogen first, two antidepressants second and everything else third. The ranking rests on a review of 90 randomized trials published alongside it. That review is frank about what the trials leave out: they were short, they say little about long-term harm, and they rarely tested one drug against another.

What the hot flash guideline recommends

Doctors call hot flashes and night sweats vasomotor symptoms. The review opens with the plain fact: vasomotor symptoms (VMS) are common in perimenopausal and postmenopausal females. Perimenopause is the stretch of years before periods stop for good.

How common is worth a number. The college says they affect up to 80% of females. A pooled analysis of population surveys published in September arrived at somewhat lower figures. Forty-one studies (n = 28,955) were included, and its estimates ranged from 54.29% in Africa to 74.23% in the Americas and Europe.

The guideline sets out three tiers.

Tier	Treatment	Strength of the recommendation
First	Estrogen with a progestogen for women with a uterus; estrogen alone for women without one	Strong, on high-certainty evidence
Second	Venlafaxine or desvenlafaxine	Conditional, on moderate-certainty evidence
Third	Escitalopram or paroxetine; gabapentin; elinzanetant or fezolinetant	Conditional, on low-to-moderate-certainty evidence

The top tier is the only one the college states firmly. A conditional recommendation, the label on the other two, is one that depends more on a woman’s circumstances and preferences. ACP recommends that clinicians initiate one of the following (strong recommendation): estrogen in combination with progestogen in females with a uterus, or estrogen alone for those who have had the uterus removed. A progestogen is a hormone added to protect the lining of the womb, which estrogen by itself can overstimulate.

The lower tiers are for women who cannot take estrogen or do not get on with it. The second applies in females who have contraindications to or do not tolerate first-line treatment, a contraindication being a medical reason not to use a drug. Venlafaxine and desvenlafaxine belong to a family of antidepressants.

The third tier mixes old and new: selective serotonin reuptake inhibitors, either escitalopram or paroxetine, which are also antidepressants; gabapentin, a nerve-pain and seizure drug; and the two recent arrivals, elinzanetant and fezolinetant.

The college explained its reasoning in one line. ACP concluded that estrogen in combination with progestogen and estrogen monotherapy had the most favorable benefits compared with harms. Monotherapy means a single drug used alone.

Its president, Jan K. Carney, put the case for acting at all. “Too many females silently suffer from disruptive hot flashes and night sweats without ever receiving effective treatment,” Carney said.

What the review of 90 trials found

The review behind the guideline was led by Susan Diem and was paid for by the college. It searched for trials up to March this year. Ninety trials were included.

Its central result is a split between two things a treatment can do: make hot flashes less frequent, and make them less severe.

Estrogen did both. So did a pill that pairs estrogen with a second compound, and oxybutynin, a bladder medicine. Compared with placebo, the review found, each reduced VMS frequency and severity.

A longer list of drugs did only the first. Compared with placebo, neurokinin receptor antagonists (NKRAs), serotonin-norepinephrine reuptake inhibitors (SNRIs), selective serotonin reuptake inhibitors (SSRIs), gabapentin, and progestogens reduced VMS frequency but not severity. The neurokinin receptor antagonists are the new non-hormonal pills. The other two long names are the antidepressant families in tiers two and three.

That difference separates estrogen from most of the alternatives ranked below it. A woman on one of the alternatives could expect fewer episodes, on this evidence, without each one being milder.

The form of estrogen mattered less than the amount. Estrogen efficacy varied by dose but not route, route meaning whether it is swallowed or absorbed through the skin.

Several treatments also helped with the knock-on effects. Estrogens, the newer pills and both antidepressant families improved scores for quality of life, and gabapentin, the newer pills, oxybutynin and the antidepressants improved sleep.

The reviewers graded how far each conclusion could be trusted. For most comparisons the certainty was low to moderate.

Where the newer non-hormonal drugs fit

The two newest drugs block a signal in the part of the brain that controls body temperature. Their trials show what a reduction in frequency looks like in practice.

Elinzanetant was tested in two trials reported in JAMA in 2024. They enrolled postmenopausal participants aged 40 to 65 years experiencing moderate to severe vasomotor symptoms, and at the start those women were having between 13 and 16 episodes a day. After 12 weeks, women on the drug were having about 3.2 fewer episodes a day than women on placebo, in both trials. Elinzanetant improved sleep disturbances and menopause-related quality of life at week 12.

Fezolinetant reached the market first. Its main trial, in The Lancet in 2023, enrolled women with an average of seven or more moderate-to-severe hot flashes per day at 97 sites in seven countries. The authors described the gap the drug class was meant to fill: options are scarce for those who cannot or do not want to take hormone therapy. That trial was paid for by the drug’s maker, Astellas Pharma.

A placebo comparison lasted 12 weeks in each of those trials. That is long enough to show that a drug reduces hot flashes and too short to show much else.

The college’s reviewers also looked at cost. They judged estrogen, with or without a progestogen, to be of high economic value, and fezolinetant to be of low value. That weighs in the ranking too: the new pills sit in the third tier beside drugs that have been available cheaply for decades.

Why hormone therapy comes with conditions

The first-line recommendation comes with qualifications. A report on the guideline by Healio, a medical news service, sets out the considerations its authors attach.

Age and timing are the main ones. The guideline’s authors noted that it is common in clinical practice to avoid initiating estrogen treatment (alone or alongside progestogen) in women aged older than 60 years, or more than ten years past their final period, and to limit treatment to three to five years.

Medical history is another. The authors advise that a history or higher risk of heart disease, breast or womb cancer, stroke or blood clots may change the balance of benefit and harm.

And there is a practical point about bleeding. Estrogen treatment, the authors wrote, “may lead to changes in vaginal bleeding pattern and abnormal withdrawal bleeding or flow, which may require further evaluation”.

The guideline arrives after a change in how regulators describe these products. According to the same report, warnings about heart disease, breast cancer and probable dementia were removed from six products following an FDA panel discussion in July 2025. The FDA is the US Food and Drug Administration.

For any choice, the college asks for a conversation. Clinicians should use an informed decision-making approach and discuss benefits, harms, contraindications, comorbid conditions, values and preferences, financial burden, and access to and availability of treatments. Comorbid conditions are a person’s other illnesses.

It also asks doctors to raise the subject. ACP encourages physicians to ask their female patients about their experience with menopausal VMS, as they may not initiate these discussions on their own.

What outside experts said about the guideline

An editorial published with the guideline came from two menopause specialists, Regina Castaneda of Mayo Clinic and Stephanie Faubion, medical director of The Menopause Society. They welcomed it, writing that it “is timely given the rapidly evolving therapeutic landscape in the management of menopause symptoms”.

They pushed back on two of the customary limits. The first is the age cut-off. A woman whose menopause came late may be past 60 and still within ten years of it. “Thus, age over 60 years should not be used as an absolute contraindication,” they wrote.

The second is the time limit on treatment. “Additionally, while a 3- to 5-year duration is commonly referenced, the available evidence does not allow definition of a duration beyond which the balance of benefits and harms changes,” they wrote.

Their overall verdict was that the guidance “offers a strong foundation for individualizing treatment of menopausal women and clarifies evidence gaps that remain”.

What the trials behind the guideline cannot show

The review lists its own limits, and they bear on the question most women ask first.

Long-term harm. Few serious problems turned up in the trials, but the trials were not built to find them. In the reviewers’ words, most studies were short-term and were not designed to evaluate serious adverse events or long-term harms. An adverse event is any medical problem recorded during a study.

The studies that might answer that. Risks such as blood clots and breast cancer emerge over years and are usually studied by following large numbers of women in ordinary care. The review set those aside: observational studies that could address long-term harms were not included. Its picture of harm is therefore narrower than its picture of benefit.

Comparisons. Almost every trial tested a drug against a placebo. The review is blunt about the result: harms data were limited. Little comparative information exists. The ranking of one drug above another rests on separate trials set side by side.

What women want. The reviewers looked for studies of how women weigh these treatments and found too little to draw on. Evidence was insufficient for patient values and preferences.

Certainty. Outside the first tier, the evidence was graded low to moderate.

Who paid. The review was funded by the college that wrote the guideline. The trials of the newer drugs were funded by their makers.

Whether to treat hot flashes, and with what, depends on a woman’s symptoms, age and medical history, which is assessed by her doctor. Do not stop or change a prescribed medicine without talking to your doctor.

A US physicians’ guideline now ranks estrogen as the first drug treatment for hot flashes and night sweats, on a review of 90 trials in which it reduced both their frequency and their severity, while most alternatives reduced frequency alone and the trials were too short to settle questions of long-term harm.